title: Automated four-color interphase fluorescence in situ hybridization approach for the simultaneous detection of specific aneuploidies of diagnostic and prognostic significance in high hyperdiploid acute lymphoblastic leukemia.
abstract: In high hyperdiploid acute lymphoblastic leukemia (ALL), the concurrence of specific trisomies confers a more favorable outcome than hyperdiploidy alone. Interphase fluorescence in situ hybridization (FISH) complements conventional cytogenetics (CC) through its sensitivity and ability to detect chromosome aberrations in nondividing cells. To overcome the limits of manual I-FISH, we developed an automated four-color I-FISH approach and assessed its ability to detect concurrent aneuploidies in ALL. I-FISH was performed using centromeric probes for chromosomes 4, 6, 10, and 17. Parameters established for nucleus selection and signal detection were evaluated. Cutoff values were determined. Combinations of aneuploidies were considered relevant when each aneuploidy was individually significant. Results obtained in 10 patient samples were compared with those obtained with CC. Various combinations of aneuploidies were identified. All clones detected by CC were observed also by I-FISH, and I-FISH revealed numerous additional abnormal clones in all patients, ranging from < or =1% to 31.6% of cells analyzed. We conclude that four-color automated I-FISH permits the identification of concurrent aneuploidies of potential prognostic significance. Large numbers of cells can be analyzed rapidly. The large number of nuclei scored revealed a high level of chromosome variability both at diagnosis and relapse, the prognostic significance of which is of considerable clinical interest and merits further evaluation.
authors.affiliation: Cancer Cytogenetics Unit, Medical Genetics Service, University Hospital and University of Lausanne (CHUV-UNIL), Lausanne, Switzerland.
authors.forename: Anna Talamo
authors.initials: AT
authors.lastname: Blandin
authors.forename: Dominique
authors.initials: D
authors.lastname: Mühlematter
authors.forename: Sandrine
authors.initials: S
authors.lastname: Bougeon
authors.forename: Céline
authors.initials: C
authors.lastname: Gogniat
authors.forename: Sarah
authors.initials: S
authors.lastname: Porter
authors.forename: Valérie
authors.initials: V
authors.lastname: Beyer
authors.forename: Valérie
authors.initials: V
authors.lastname: Parlier
authors.forename: Jacques S
authors.initials: JS
authors.lastname: Beckmann
authors.forename: Guy
authors.initials: G
authors.lastname: van Melle
authors.forename: Martine
authors.initials: M
authors.lastname: Jotterand
mesh_terms: D000293:Adolescent; D000328:Adult; D000782:Aneuploidy; D002675:Child, Preschool; D002869:Chromosome Aberrations; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D007399:Interphase; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D011379:Prognosis; D012680:Sensitivity and Specificity; D014314:Trisomy